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1.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445088

RESUMO

Improving the therapeutic characteristics of antibiotics is an effective strategy for controlling the growth of multidrug-resistant Gram-negative microorganisms. The purpose of this study was to develop a colistin (CT) delivery system based on hyaluronic acid (HA) and the water-soluble cationic chitosan derivative, diethylaminoethyl chitosan (DEAECS). The CT delivery system was a polyelectrolyte complex (PEC) obtained by interpolymeric interactions between the HA polyanion and the DEAECS polycation, with simultaneous inclusion of positively charged CT molecules into the resulting complex. The developed PEC had a hydrodynamic diameter of 210-250 nm and a negative surface charge (ζ-potential = -19 mV); the encapsulation and loading efficiencies were 100 and 16.7%, respectively. The developed CT delivery systems were characterized by modified release (30-40% and 85-90% of CT released in 15 and 60 min, respectively) compared to pure CT (100% CT released in 15 min). In vitro experiments showed that the encapsulation of CT in polysaccharide carriers did not reduce its antimicrobial activity, as the minimum inhibitory concentrations against Pseudomonas aeruginosa of both encapsulated CT and pure CT were 1 µg/mL.


Assuntos
Antibacterianos/administração & dosagem , Quitosana/química , Colistina/administração & dosagem , Portadores de Fármacos/química , Ácido Hialurônico/química , Polieletrólitos/química , Antibacterianos/farmacologia , Colistina/farmacologia , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos
2.
Int J Mol Sci ; 22(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34445587

RESUMO

Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are encapsulated in the microspheres to increase their bioavailability and provide a long release period (days or months) with constant drug plasma concentration. The biodegradable and biocompatible properties of PLGA/PLA polymers, including but not limited to molecular weight, end group, lactide to glycolide ratio, and minor manufacturing changes, could greatly affect the quality attributes of microsphere formulations such as release profile, size, encapsulation efficiency, and bioactivity of biopharmaceuticals. Besides, the encapsulated proteins/peptides are susceptible to harsh processing conditions associated with microsphere fabrication methods, including exposure to organic solvent, shear stress, and temperature fluctuations. The protein/peptide containing LAI microspheres in clinical use is typically prepared by double emulsion, coacervation, and spray drying techniques. The purpose of this review is to provide an overview of the formulation attributes and conventional manufacturing techniques of LAI microspheres that are currently in clinical use for protein/peptides. Furthermore, the physicochemical characteristics of the microsphere formulations are deliberated.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Microesferas , Fragmentos de Peptídeos/administração & dosagem , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas/administração & dosagem , Animais , Composição de Medicamentos , Humanos , Fragmentos de Peptídeos/química , Proteínas/química
3.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361825

RESUMO

Lipid-based nanocarriers (LNs) have made it possible to prolong corneal residence time and improve the ocular bioavailability of ophthalmic drugs. In order to investigate how the LNs interact with the ocular mucosa and reach the posterior eye segment, we have formulated lipid nanocarriers that were designed to bear a traceable fluorescent probe in the present work. The chosen fluorescent probe was obtained by a conjugation reaction between fluoresceinamine and the solid lipid excipient stearic acid, forming a chemically synthesized adduct (ODAF, N-(3',6'-dihydroxy-3-oxospiro [isobenzofuran-1(3H),9'-[9H] xanthen]-5-yl)-octadecanamide). The novel formulation (LN-ODAF) has been formulated and characterized in terms of its technological parameters (polydispersity index, mean particle size and zeta potential), while an in vivo study was carried out to assess the ability of LN-ODAF to diffuse through different ocular compartments. LN-ODAF were in nanometric range (112.7 nm ± 0.4), showing a good homogeneity and long-term stability. A TEM (transmission electron microscopy) study corroborated these results of characterization. In vivo results pointed out that after ocular instillation, LN ODAF were concentrated in the cornea (two hours), while at a longer time (from the second hour to the eighth hour), the fluorescent signals extended gradually towards the back of the eye. From the results obtained, LN-ODAF demonstrated a potential use of lipid-based nanoparticles as efficient carriers of an active pharmaceutical ingredient (API) involved in the management of retinal diseases.


Assuntos
Córnea/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipídeos/química , Nanopartículas/administração & dosagem , Segmento Posterior do Olho/metabolismo , Compostos de Espiro/administração & dosagem , Animais , Córnea/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Segmento Posterior do Olho/efeitos dos fármacos , Coelhos , Compostos de Espiro/química
4.
ACS Appl Mater Interfaces ; 13(33): 39003-39017, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433253

RESUMO

Improving tumor immunogenicity is critical for increasing the responsiveness of triple-negative breast cancer (TNBC) to anti-PD-(L)1 treatment. Here, we verified that chidamide (CHI), an epigenetic modulator, could elicit immunogenic cell death within TNBC to enhance cancer immunogenicity and elicit an antitumor immune response. Additionally, CHI increased the expression level of PD-L1, MHC I, and MHC II on cancer cells, which contributed to T-cell recognition and PD-1/PD-L1 blockade therapy response. The synergistic antitumor efficacy of CHI and PD-L1 blockade therapy was further explored through liposomes co-delivering CHI and BMS-202 (a small-molecule PD-L1 inhibitor). The liposomes possessed good biocompatibility, security, and controllable drug release and endowed therapeutics drugs with favorable tumor accumulation. Furthermore, the drug-loaded liposomes could obviously boost the antitumor immunity of TNBC through CHI-enhanced tumor immunogenicity and BMS-202-mediated PD-L1 blockade, thereby effectively inhibiting the growth of primary and metastatic tumors with an inhibitory rate of metastasis of up to 96%. In summary, this work provided a referable and optional approach for clinical antitumor therapy based on the combination of an epigenetic modulator and PD-1/PD-L1 blockade therapy.


Assuntos
Acetamidas/química , Aminopiridinas/química , Antineoplásicos/farmacologia , Benzamidas/química , Portadores de Fármacos/química , Inibidores de Checkpoint Imunológico/química , Piridinas/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/imunologia , Acetamidas/farmacologia , Aminopiridinas/farmacologia , Animais , Benzamidas/farmacologia , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Terapia Combinada/métodos , Liberação Controlada de Fármacos , Epigênese Genética/efeitos dos fármacos , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia/métodos , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Piridinas/farmacologia , Bibliotecas de Moléculas Pequenas/química , Distribuição Tecidual , Resultado do Tratamento
5.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443323

RESUMO

Polysaccharides are a versatile class of macromolecules that are involved in many biological interactions critical to life. They can be further modified for added functionality. Once derivatized, these polymers can exhibit new chemical properties that can be further optimized for applications in drug delivery, wound healing, sensor development and others. Chitosan, derived from the N-deacetylation of chitin, is one example of a polysaccharide that has been functionalized and used as a major component of polysaccharide biomaterials. In this brief review, we focus on one aspect of chitosan's utility, namely we discuss recent advances in dual-responsive chitosan hydrogel nanomaterials.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Hidrogéis/química , Nanocompostos/química , Animais , Humanos
6.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443336

RESUMO

We develop a suitable delivery system for niaouli essential oil (NEO) using a nanoemulsification method for acne vulgaris. Prepared nanoemulsions (NEs) were characterized for droplet dimension, rheology, surface charge, and stability. The ability of NEO formulations against Propionibacterium acnes and Staphylococcus epidermidis was investigated and all formulations showed antiacne potential in vitro. Ex vivo permeation studies indicated significant improvement in drug permeations and steady state flux of all NEO-NEs compared to the neat NEO (p < 0.05). On the basis of the studied pharmaceutical parameters, enhanced ex vivo skin permeation, and marked effect on acne pathogens, formulation NEO-NE4 was found to be the best (oil (NEO; 10% v/v); Kolliphor EL (9.25% v/v), Carbitol (27.75% v/v), and water (53% v/v)). Concisely, the in vitro and ex vivo results revealed that nanoemulsification improved the delivery as well as bioactivities of NEO significantly.


Assuntos
Portadores de Fármacos/química , Melaleuca/química , Nanoestruturas/química , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Emulsões , Óleos Voláteis/metabolismo , Permeabilidade , Pele/metabolismo , Staphylococcus epidermidis/efeitos dos fármacos
7.
Molecules ; 26(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34443357

RESUMO

In this work, we propose the utilization of scCO2 to impregnate ibuprofen into the mcl-PHA matrix produced by Pseudomonas chlororaphis subs. aurantiaca (DSM 19603). The biopolymer has adhesive properties, is biocompatible and has a melting temperature of 45 °C. Several conditions, namely, pressure (15 and 20 MPa) and impregnation time (30 min, 1 h and 3 h) were tested. The highest ibuprofen content (90.8 ± 6.5 mg of ibuprofen/gPHA) was obtained at 20 MPa and 40 °C, for 1 h, with an impregnation rate of 89 mg/(g·h). The processed mcl-PHA samples suffered a plasticization, as shown by the decrease of 6.5 °C in the Tg, at 20 MPa. The polymer's crystallinity was also affected concomitantly with the matrices' ibuprofen content. For all the impregnation conditions tested the release of ibuprofen from the biopolymer followed a type II release profile. This study has demonstrated that the mcl-PHA produced by P. chlororaphis has a great potential for the development of novel topical drug delivery systems.


Assuntos
Dióxido de Carbono/química , Portadores de Fármacos/química , Ibuprofeno/química , Poli-Hidroxialcanoatos/química , Adesividade , Liberação Controlada de Fármacos , Temperatura
8.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443551

RESUMO

Hot-melt extrusion (HME) has great advantages for the preparation of solid dispersion (SD), for instance, it does not require any organic solvents. Nevertheless, its application to high-melting-point and thermosensitive drugs has been rarely reported. In this study, thermally unstable curcumin (Cur) was used as a drug model. The HME process was systematically studied by adjusting the gradient temperature mode and residence time, with the content, crystallinity and dissolution of Cur as the investigated factors. The effects of barrel temperature, screw speed and cooling rate on HME were also examined. Solubility parameters and the Flory-Huggins method were used to evaluate the miscibility between Cur and carriers. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, equilibrium solubility and in vitro and in vivo experiments were used to characterize and evaluate the results. An amorphous Cur SD was successfully obtained, increasing the solubility and release of Cur. In the optimal process, the mass ratio of Cur to Eudragit® E PO (EPO) was 1:4 and the barrel temperature was set at a gradient heating mode (130 °C-135 °C-140 °C-145 °C-150 °C-155 °C-160 °C) at 100 rpm. Related pharmacokinetic test results also showed the improved bioavailability of the drug in rats. In a pharmacodynamic analysis of Sprague-Dawley rats, the Cmax and the bioavailability of the Cur-EPO SD were 2.6 and 1.5 times higher than those of Cur, respectively. The preparation of the amorphous SD not only provided more solubility but also improved the bioavailability of Cur, which provides an effective way to improve the bioavailability of BCS II drugs.


Assuntos
Curcumina/química , Portadores de Fármacos/química , Temperatura Alta , Ácidos Polimetacrílicos/química , Disponibilidade Biológica , Curcumina/farmacocinética , Transição de Fase
9.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443569

RESUMO

This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic-hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.


Assuntos
Tecnologia de Extrusão por Fusão a Quente , Resveratrol/química , Resveratrol/farmacocinética , Disponibilidade Biológica , Preparações de Ação Retardada , Portadores de Fármacos/química , Temperatura Alta , Interações Hidrofóbicas e Hidrofílicas , Polietilenoglicóis/química , Solubilidade
10.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360758

RESUMO

The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of -40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078-0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.


Assuntos
Antioxidantes , Curcumina , Portadores de Fármacos , Nanoestruturas , Animais , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Disponibilidade Biológica , Linhagem Celular Tumoral , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Emulsões , Humanos , Masculino , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Projetos Piloto , Ratos , Ratos Sprague-Dawley
11.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445639

RESUMO

Nanoparticles bearing specific targeting groups can, in principle, accumulate exclusively at lesion sites bearing target molecules, and release therapeutic agents there. However, practical application of targeted nanoparticles in the living organism presents challenges. In particular, intravasally applied nanoparticles encounter physical and physiological barriers located in blood vessel walls, blocking passage from the blood into tissue compartments. Whereas small molecules can pass out of the blood, nanoparticles are too large and need to utilize physiological carriers enabling passage across endothelial walls. The issues associated with crossing blood-tissue barriers have limited the usefulness of nanoparticles in clinical applications. However, nanoparticles do not encounter blood-tissue barriers if their targets are directly accessible from the blood. This review focuses on osteoporosis, a disabling and common disease for which therapeutic strategies are limited. The target sites for therapeutic agents in osteoporosis are located in bone resorption pits, and these are in immediate contact with the blood. There are specific targetable biomarkers within bone resorption pits. These present nanomedicine with the opportunity to treat a major disease by use of simple nanoparticles loaded with any of several available effective therapeutics that, at present, cannot be used due to their associated side effects.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanomedicina , Nanopartículas/administração & dosagem , Osteoporose/tratamento farmacológico , Idoso , Humanos , Nanopartículas/química
12.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445466

RESUMO

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core-shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core-shell microparticles were of spherical appearance, with an average size of 14.65 µm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core-shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Microesferas , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Apoptose , Proliferação de Células , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Camundongos , Paclitaxel/administração & dosagem , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445521

RESUMO

Poly(aspartamide) derivatives, one kind of amino acid-based polymers with excellent biocompatibility and biodegradability, meet the key requirements for application in various areas of biomedicine. Poly(aspartamide) derivatives with stimuli-responsiveness can usually respond to external stimuli to change their chemical or physical properties. Using external stimuli such as temperature and pH as switches, these smart poly(aspartamide) derivatives can be used for convenient drug loading and controlled release. Here, we review the synthesis strategies for preparing these stimuli-responsive poly(aspartamide) derivatives and the latest developments in their applications as drug carriers.


Assuntos
Ácido Aspártico/análogos & derivados , Portadores de Fármacos/síntese química , Polímeros/síntese química , Ácido Aspártico/síntese química , Ácido Aspártico/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Polímeros/química , Temperatura
14.
Molecules ; 26(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34361575

RESUMO

Glass ionomer cements and resin-based composites are promising materials in restorative dentistry. However, their limited mechanical properties and the risk of bulk/marginal fracture compromise their lifespan. Intensive research has been conducted to understand and develop new materials that can mimic the functional behavior of the oral cavity. Nanotechnological approaches have emerged to treat oral infections and become a part of scaffolds for tissue regeneration. Carbon nanotubes are promising materials to create multifunctional platforms for dental applications. This review provides a comprehensive survey of and information on the status of this state-of-the-art technology and describes the development of glass ionomers reinforced with carbon nanotubes possessing improved mechanical properties. The applications of carbon nanotubes in drug delivery and tissue engineering for healing infections and lesions of the oral cavity are also described. The review concludes with a summary of the current status and presents a vision of future applications of carbon nanotubes in the practice of dentistry.


Assuntos
Portadores de Fármacos , Teste de Materiais , Nanotubos de Carbono/química , Cimentos de Resina , Resinas Acrílicas/química , Resinas Acrílicas/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Humanos , Cimentos de Resina/química , Cimentos de Resina/uso terapêutico , Dióxido de Silício/química , Dióxido de Silício/uso terapêutico , Propriedades de Superfície
15.
Molecules ; 26(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34361636

RESUMO

Naturally-occurring halloysite nanotubes (HNTs) have many advantages for constructing target-specific delivery of phototherapeutic agents. Here, HNTs were labeled with fluorescein isothiocyanate (FITC) and loaded with the type-II photosensitizer indocyanine green (ICG) for phototherapy. HNTs-FITC-ICG was structurally stable due to presence of HNTs as the nanocarrier and protective agent. The nanocarrier was further wrapped with red blood cell membrane (RBCM) to enhance the biocompatibility. The HNTs-FITC-ICG-RBCM nanocarrier show high cytocompatibility and hemocompatibility. Due to the photothermal effect of ICG, a significant temperature rising was achieved by irradiation of the nanocarrier using 808 nm laser. The photothermal temperature rising was used to kill the cancer cells effectively. The HNTs-FITC-ICG-RBCM nanocarrier was further linked with anti-EpCAM to endow it with targeting therapy performance against breast cancer, and the anti-EpCAM-conjugated nanocarrier exhibited significantly tumor-specific accumulation. The RBCM-coated and biocompatible HNTs nanocarrier is a promising candidate for target-specific therapy of cancer.


Assuntos
Membrana Celular/química , Argila/química , Materiais Revestidos Biocompatíveis , Portadores de Fármacos , Nanotubos/química , Neoplasias , Terapia Fototérmica , Animais , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Coelhos
16.
Molecules ; 26(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34443412

RESUMO

Palmarosa essential oil (PEO) is an alternative to synthetic fungicides to control the contamination by food-deteriorating fungi, such as Aspergillus nomius. Nonetheless, the low long-term stability and volatility hamper its utilization. Thus, this study aimed to develop nanostructured lipid carriers (NLCs) containing PEO to improve its stability and consequently prolong the activity against A. nomius. A mixture design was applied to find the best preparation conditions for antifungal activity. The characterization analyses included size measurements, zeta potential (ζ-potential), entrapment efficiency (EE), and antifungal activity (by inhibition of mycelial growth (IMG) and/or in situ test (pre-contaminated Brazil nuts) tests). The nanocarriers presented particle sizes smaller than 300 nm, homogeneous size distribution, ζ-potential of -25.19 to -41.81 mV, and EE between 73.6 and 100%. The formulations F5 and F10 showed the highest IMG value (98.75%). Based on the regression model, three optimized formulations (OFs) were tested for antifungal activity (IMG and in situ test), which showed 100% of inhibition and prevented the deterioration of Brazil nuts by A. nomius. The preliminary stability test showed the maintenance of antifungal activity and physicochemical characteristics for 90 days. These results suggest a promising system as a biofungicide against A. nomius.


Assuntos
Aspergillus/efeitos dos fármacos , Cymbopogon/química , Portadores de Fármacos/química , Nanoestruturas/química , Óleos Voláteis/farmacologia , Antifúngicos/farmacologia , Bertholletia/microbiologia , Composição de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
17.
Molecules ; 26(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34443443

RESUMO

Cytostatic chemotherapeutics provide a classical means to treat cancer, but conventional treatments have not increased in efficacy in the past years, warranting a search for new approaches to therapy. The aim of the study was, therefore, to obtain methacrylic acid (MAA) (co)polymers and to study their immunopharmacological properties. 4-Cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl] pentanoic acid (CDSPA) and 2-cyano-2-propyl dodecyl trithiocarbonate (CPDT) were used as reversible chain transfer agents. Experiments were carried out in Wistar rats. The MTT assay was used to evaluate the cytotoxic effect of the polymeric systems on peritoneal macrophages. An experimental tumor model was obtained by grafting RMK-1 breast cancer cells. Serum cytokine levels of tumor-bearing rats were analyzed. The chain transfer agents employed in classical radical polymerization substantially reduced the molecular weight of the resulting polymers, but a narrow molecular weight distribution was achieved only with CDSPA and high CPDT concentrations. Toxicity was not observed when incubating peritoneal macrophages with polymeric systems. In tumor-bearing rats, the IL-10 concentration was 1.7 times higher and the IL-17 concentration was less than half that of intact rats. Polymeric systems decreased the IL-10 concentration and normalized the IL-17 concentration in tumor-bearing rats. The maximum effect was observed for a MAA homopolymer with a high molecular weight. The anion-active polymers proposed as carrier constituents are promising for further studies and designs of carrier constituents of drug derivatives.


Assuntos
Antineoplásicos/imunologia , Antineoplásicos/farmacologia , Portadores de Fármacos/química , Ácidos Polimetacrílicos/farmacologia , Animais , Antineoplásicos/administração & dosagem , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Citocinas/metabolismo , Feminino , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Peso Molecular , Ácidos Polimetacrílicos/administração & dosagem , Ratos Wistar
18.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445799

RESUMO

Concerns associated with nanocarriers' therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.


Assuntos
Portadores de Fármacos/química , Ácidos Nucleicos/química , Ácidos Nucleicos Peptídicos/química , Peptídeos/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Nanopartículas/química
19.
ACS Appl Mater Interfaces ; 13(33): 39934-39948, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34396771

RESUMO

There are two severe obstacles in cancer immunotherapy. The first is that the low response rate challenges the immune response owing to the immunosuppressive tumor microenvironment (ITM) and poor immunogenicity of the tumor. The second obstacle is that the dense and intricate pathophysiology barrier seriously restricts deep drug delivery in solid tumors. A laser/glutathione (GSH)-activatable nanosystem with tumor penetration for achieving highly efficient immunotherapy is reported. The core of the nanosystem was synthesized by coordinating zinc ions with GSH-activatable oxaliplatin (OXA) prodrugs and carboxylated phthalocyanine. Such an OXA/phthalocyanine-based coordination polymer nanoparticle (OPCPN) was wrapped by a phospholipid bilayer and NTKPEG. NTKPEG is a PEGylated indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor prodrug containing a thioketal (TK) linker, which was modified on the OPCPN (OPCPN@NTKPEG). Upon the laser irradiation tumor site, ROS production of the OPCPN@NTKPEG triggers cleavage of NTKPEG by degradation of TK for promoted tumor penetration and uptake. OXA, phthalocyanine, and IDO1 inhibitor were released by the intracellular high-level GSH. OXA inhibits cell growth and is combined with photodynamic therapy (PDT) to induce immunogenic cell death (ICD). The IDO1 inhibitor reversed the ITM by suppressing IDO1-mediated Trp degradation and exhaustion of cytotoxic T cells. Laser/GSH-activatable drug delivery was more conducive to enhancing ICD and reversing ITM in deep tumors. Chemo-PDT with OPCPN@NTKPEG significantly regressed tumor growth and reduced metastasis by improved cancer immunotherapy.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Glutationa/química , Indóis/química , Nanopartículas/química , Oxaliplatina/química , Fármacos Fotossensibilizantes/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Glutationa/metabolismo , Humanos , Morte Celular Imunogênica/efeitos dos fármacos , Morte Celular Imunogênica/efeitos da radiação , Imunoterapia , Indóis/farmacocinética , Lasers , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Oxaliplatina/farmacocinética , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacocinética , Polietilenoglicóis/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Distribuição Tecidual , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação
20.
ACS Appl Mater Interfaces ; 13(33): 38969-38978, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34399054

RESUMO

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up" without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.


Assuntos
Anti-Hipertensivos/química , Doença das Coronárias/tratamento farmacológico , Portadores de Fármacos/química , Excipientes/química , Indóis/química , Polímeros/química , Anti-Hipertensivos/farmacologia , Dioxanos/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Indóis/farmacologia , Metacrilatos/química , Transição de Fase , Poliésteres/química , Impressão Tridimensional , Pirrolidinonas/química , Relação Estrutura-Atividade
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